Genetic studies have shown an association between multiple autoim

Genetic studies have shown an association between multiple autoimmune diseases and

TNFAIP3 (A20) and TNIP1 (ABIN1), both repressors of NF-B and of IKBKE (IKK epsilon), which is an NF-B activator. The aim of this study was to analyse single nucleotide polymorphisms (SNPs) in the IKBKE, NFKB1, TNIP1 and TNFAIP3 genes for association with primary SS. A total of 12 SNPs were genotyped in 1105 patients from Scandinavia (Sweden and Norway, n=684) and the UK (n=421) and 4460 controls (Scandinavia, n=1662, UK, n=2798). When patients were stratified for the presence of anti-SSA and/or anti-SSB antibodies (n=868), case-control meta-analysis found an association between antibody-positive primary SS and two SNPs in TNIP1 (P=3.4×10(-5), OR=1.33, 95%CI: 1.16-1.52 for rs3792783 and P=1.3×10(-3), OR=1.21, 95%CI: 1.08-1.36 for rs7708392). this website A TNIP1 risk haplotype was associated with antibody-positive primary SS (P=5.7×10(-3), OR=1.47, 95%CI: 1.12-1.92). There were no significant associations with IKBKE, NFKB1 or

TNFAIP3 in the meta-analysis of the Scandinavian and UK cohorts. We conclude that polymorphisms in TNIP1 are associated with antibody-positive primary SS.”
“Current theories of multiple sclerosis (MS) induction and progression place autoreactive T cells in the focus of the pathogenesis. Mesenchymal/stromal stem cells (MSC) have become a promising alternative approach for pathogenic therapy of MS due to their immunomodulatory properties, underlying mechanisms of which are intensive BI 2536 purchase study. www.selleck.co.jp/products/Y-27632.html The objective

of the research was to investigate the contribution of PGE(2) to MSC-mediated suppression in patients with MS using in vitro model of mitogen- and myelin-stimulated T cell cocultivation with autologous/allogeneic MSC. We have showed that PGE(2) production depends on cell-to-cell contact of MSC and lymphocytes. The antigenic stimulation did not affect PGE(2) production following cocultivation of MSC and PBMC, and it is the presence of MSC in cell culture that significantly increases PGE(2) production irrespective of antigenic cultivation conditions. Simultaneously, PGE(2) synthesis correlated with indexes of MSC-mediated suppression of mitogen- and myelin-stimulated T cell proliferation in patients with MS. No significant differences in PGE(2) production by autologous and allogeneic MSC have been established. These results have demonstrated that in patients with MS, PGE(2) is one of the possible factors of MSC immunosuppression. The interrelation between PGE(2) concentrations and T cell proliferation suppression mediated by MSC may explain one of the immune mechanisms of cell therapy, which is crucial for the further proper use of MSC in MS research and pathogenic treatment.”
“In this study, we report the clinical and genetic features of Chinese patients with X-linked lymphoproliferative syndrome (XLP).

This effect does not seem to involve acetylcholine-stimulated nit

This effect does not seem to involve acetylcholine-stimulated nitric oxide release.

Copyright (C) 2008 S. Karger JQ1 cell line AG, Basel.”
“Microglial cell activation and migration play an important role in neuroinflammation propagation. While it is known that the lipid transmitter palmitoylethanolamide (PEA) regulates microglial migration by interacting with a cannabinoid-like receptor, the production and inactivation of this lipid by microglia has never been addressed directly. Here we show that the mouse microglial cell line BV-2 produces and hydrolyzes PEA. The carbamate compound URB602 inhibits PEA hydrolysis in BV-2 cell homogenates and increases PEA levels in intact cells, whereas the FAAH inhibitor URB597 and serine-hydrolase inhibitor MAFP do not affect PEA levels

in intact cells. This unique pharmacological profile of inhibitors on PEA hydrolysis suggests the involvement of a previously undescribed enzyme that degrades PEA. This enzyme expressed by microglia constitutes a promising target for controlling the propagation of neuroinflammation. Published by Elsevier Ltd.”
“The activity of NADPH oxidase (NOX) is blocked by nitric oxide (NO). Hydrogen sulfide (H2S) Crenolanib manufacturer is also produced by blood vessels. It is reasonable to suggest that H2S may have similar actions to NO on NOX. In order to test this hypothesis, the effect of sodium hydrosulfide (NaHS) on O-2(-) formation, the expression of NOX-1 (a catalytic subunit of NOX) and Rac(1) activity (essential for full NOX activity) in isolated vascular smooth muscle cells (hVSMCs) was investigated. hVSMCs were incubated with the thromboxane A(2) analogue U46619 +/- NaHS for 1 or 16 h, and O-2(-) formation, NOX-1 expression Roflumilast and Rac(1) activity were assessed. The

possible interaction between H2S and NO was also studied by using an NO synthase inhibitor, L-NAME, and an NO donor, DETA-NONOate. The role of K-ATP channels was studied by using glibenclamide. NaHS inhibited O-2(-) formation following incubation of 1 h (IC 50, 30 nM) and 16 h (IC 50, 20 nM), blocked NOX-1 expression and inhibited Rac(1) activity. These inhibitory effects of NaHS were mediated by the cAMP-protein-kinase-A axis. Exogenous H2S prevents NOX-driven intravascular oxidative stress through an a priori inhibition of Rac(1) and downregulation of NOX-1 protein expression, an effect mediated by activation of the adenylylcyclase-cAMP-protein-kinase-G system by H2S. Copyright (C) 2008 S. Karger AG, Basel.”
“Cannabinoid agonists regulate NO and cyclic AMP production in N18TG2 neuroblastoma cells, leading to the hypothesis that neuronal cyclic GMP production could be regulated by CB1 cannabinoid receptors. NO (nitric oxide)- sensitive guanylyl cyclase (GC) is a heterodimeric cytosolic protein that mediates the down-stream effects of NO.

On the two protocols conducted in the 1990s, EFS was 79-85% for T

On the two protocols conducted in the 1990s, EFS was 79-85% for T-cell ALL patients and 75-78% for adolescents (age 10-18 years). Results of randomized studies revealed that dexrazoxane prevented acute cardiac injury without adversely affecting EFS or OS in high-risk (HR) patients, and frequently

dosed intrathecal chemotherapy was an effective substitute for cranial radiation in standard-risk (SR) patients. Current studies continue to focus on improving efficacy while minimizing acute and late toxicities. Selleckchem Copanlisib Leukemia (2010) 24, 320-334; doi: 10.1038/leu.2009.253; published online 17 December 2009″
“We analyzed the long-term outcomes of 1021 patients with acute lymphoblastic leukemia (ALL), enrolled in four successive clinical trials (ALL811, ALL841, ALL874 and ALL911) between 1981 and 1993. Selleckchem Trichostatin A All patients received risk-adopted therapy according to leukocyte count and age at the time of diagnosis.

The median follow-up durations of the four studies were 17.8 years in ALL811, 15.5 years in ALL841, 11.9 years in ALL874 and 15.8 years in ALL911. Patients’ event-free survival (EFS) and overall survival (OS) rates at 12 years were 41.0 and 54.3% in ALL811, 50.2 and 60.2% in ALL841, 57.3 and 64.7% in ALL874, and 63.4 and 71.7% in ALL911, respectively. Thus, cure can become a reality for about 70% of children with ALL. There is, however, still a significant difference in survival outcomes according to risk group. Late effects were observed in 70 patients out of 834 (8.4%); hepatitis and short stature were most commonly reported. Reduction of late adverse effects for all patients and development of new treatment strategies for very-high-risk patients are major issues for upcoming trials to address. Leukemia (2010) 24, 335-344; doi: 10.1038/leu.2009.259; published online 17 December 2009″
“Analysis of 2668 children with

acute lymphoblastic leukemia (ALL) treated in two successive Nordic clinical trials (Nordic Society MRIP of Paediatric Haematology and Oncology (NOPHO) ALL-92 and ALL-2000) showed that 75% of all patients are cured by first-line therapy, and 83% are long-term survivors. Improvements in systemic and intrathecal chemotherapy have reduced the use of central nervous system (CNS) irradiation to <10% of the patients and provided a 5-year risk of isolated CNS relapse of 2.6%. Improved risk stratification and chemotherapy have eliminated the previous independent prognostic significance of gender, CNS leukemia and translocation t(1;19)(q23;p13), whereas the post-induction level of minimal residual disease (MRD) has emerged as a new risk grouping feature. Infant leukemia, high leukocyte count, T-lineage immunophenotype, translocation t(4;11)(q21;q23) and hypodiploidy persist to be associated with lower cure rates.

Materials and Methods: Between 1999 and 2007, 4,592 consecutive p

Materials and Methods: Between 1999 and 2007, 4,592 consecutive patients underwent radical prostatectomy without prior radiotherapy at our institution. Data were collected from prospective surgical and institutional morbidity databases, and retrospectively from inpatient and outpatient medical and billing records. Cases were assigned a Charlson score to account for comorbidities. Complications were graded according to the modified Clavien classification.

Results: Open radical prostatectomy was performed

in 3,458 men (75%) and laparoscopic radical prostatectomy was performed in 1,134 (25%). The laparoscopic radical prostatectomy check details group included 97 robotic-assisted cases. Median patient age was 59.5 years (IQR 54.7, 64.2). Symptomatic anastomotic strictures developed in 198 patients (4%) after a median postoperative followup of 3.5 months (IQR 2.1, 6.1). On multivariate analysis significant predictors included patient age, body mass index, Charlson score, renal insufficiency, individual surgeon, surgical approach and the presence of postoperative urine leak or hematoma.

Conclusions: Patient factors as well as technical factors influence the development of symptomatic anastomotic strictures

following contemporary radical prostatectomy. The impact of these factors is influenced by the individual surgeon and the approach used.”
“Background. We investigated whether the predictive accuracy of mild cognitive impairment (MCI) for Alzheimer-type dementia (AD) in a clinical setting is dependent on age and the definition of MCI used.

Method. Non-demented subjects older than 40 (n=320) who attended a memory AG-120 manufacturer clinic of a university Doxorubicin order hospital were reassessed 5 years later for the presence of AD. MCI was diagnosed according to the criteria of amnestic MCI, mild functional impairment (MFI), ageing-associated cognitive decline (AACD), and age-associated memory impairment (AAMI). The main outcome measure was the area under the curve (AUC) of a receiver operating characteristic (ROC) curve. Analyses were conducted on the entire sample and on subgroups of subjects aged 40-54, 55-69 and 70-85 years.

Results.

A diagnosis of AD at follow-up was made in 58 subjects. Four of them were in the 40-54 age group, 29 in the 55-69 age group and 25 in the 70-85 age group. The diagnostic accuracy in the entire sample was low to moderately high with AUCs ranging from 0.56 (AACD) to 0.75 (amnestic MCI). A good predictive accuracy with an AUC >0.80 was only observed in subjects aged 70-85 using the criteria of amnestic MCI (AUC=0.84).

Conclusions. The predictive accuracy of MCI for AD is dependent on age and the definition of MCI used. The predictive accuracy is good only for amnestic MCI in subjects 70-85 years. As subjects with prodromal AD are often younger than 70, the usefulness of MCI as predictor of AD in clinical practice is limited.

3

M NaCl intake and water intake, and bilateral injection

3

M NaCl intake and water intake, and bilateral injections of the selective mu-OR antagonist D-Phe-Cys-Trp-Arg-Thr-Pen-Thr-NH2 (CTAP) in the doses of 0.5, 1, and 2 nmol into the CeA produced a dose-related decrease of 0.3 M NaCl and water intake induced by DAMGO 2 nmol into the same site. In rats treated with the diuretic furosemide (10 mg/kg b.w.) click here combined with the angiotensin-converting enzyme inhibitor captopril (5 mg/kg b.w.) injected subcutaneously, bilateral injections of DAMGO 2 nmol into the CeA increased 0.3 M NaCl intake and water intake and the blockade of mu-ORs with CTAP 1 nmol injected into the CeA reduced the increase in 0.3 M NaCl intake and water intake induced by DAMGO 2 nmol into the same site. Bilateral injections of DAMGO into the CeA did not change urinary volume, sodium urinary excretion and mean arterial pressure, but increased activity. Thus stimulating mu-ORs in the CeA increases hypertonic sodium intake, whereas antagonizing these sites inhibits hypertonic sodium intake. Together, our results implicate mu-ORs in the CeA in a positive regulation of sodium intake. (c) 2012 IBRO. Published by Elsevier Ltd.

All rights reserved.”
“Objectives: Various types of surgical and interventional procedures have been reported to cause cardiac sympathetic denervation. We aimed at evaluating the effects of coronary artery bypass grafting (CABG) in cardiac sympathetic AZD1080 innervation through meta-iodobenzyl-guanidine (MIBG) imaging.

Methods: MIBG imaging was performed in 21 patients with coronary artery disease (CAD) 1 day before and 1 week and 6 months after CABG with concomitant Microtubule Associated measurements of corrected QT interval. In each study we evaluated MIBG defect score in a 16-segment left ventricular model, MIBG-defect size (percent) from generated polar

maps, and heart/mediastinum ratio.

Results: Mean MIBG defect score and size were increased (32 +/- 9.5 vs 24 +/- 5, P < .0001, and 49.5% +/- 20.4% vs 37% +/- 8.7%, P = .004, respectively) and mean heart/mediastinum ratio was reduced (1.5 +/- 0.4 vs 1.9 +/- 0.3, P < .0001) at 1 week after CABG. At 6 months these indices had no significant differences compared with their pre-CABG values. Mean corrected QT interval demonstrated no significant changes. Increase in MIBG score in the second imaging was associated with adverse events related to arrhythmia and myocardial dysfunction during the 6-month follow-up period in a binary logistic regression model.

Conclusions: CABG is associated with clinically important but reversible reduction in cardiac sympathetic nerve function, with periprocedural effects (cardioplegia, hypothermia, ischemia, direct nerve injury) being possible mechanisms for this finding. (J Thorac Cardiovasc Surg 2012;144:210-6)”
“Inhibition of return (IOR) is a phenomenon thought to reflect a mechanism to protect the organism from redirecting attention to previously scanned insignificant locations.

In addition, genes associated with lipid metabolism were altered

In addition, genes associated with lipid metabolism were altered by both treatments. Interestingly, only the parental compound (AA) significantly induced expression levels of genes associated with oxidative phosphorylation, in particular ATP synthase, which correlated with elevated ATP levels, indicating an increased energy demand in liver during AA exposure. Acrylamide-treated mice also showed significantly higher activity of glutathione S-transferase in association with decreased levels of reduced glutathione (GSH), which may imply an enhanced rate of conjugation of AA with GSH in liver. These results suggest different hepatic mechanisms of action

of AA and GA and provide important insights into the involvement of mitochondria during their exposures.”
“Trifluoroacetic acid is a metabolite BAY 11-7082 chemical structure of the inhaled anesthetics halothane, desflurane and isoflurane as well as a major contaminant in HPLC-purified peptides. Ligand-gated Verubecestat supplier ion channels, including cys-loop receptors such as the glycine receptor, have been the targets of peptide-based drug

design and are considered to be likely candidates for mediating the effects of anesthetics in vivo, but the possible secondary contributions of contaminants and metabolites to these effects have not been studied. We used two-electrode voltage-clamp electrophysiology to test glycine, GABA(A) and 5-HT3 receptors expressed in Xenopus oocytes for their sensitivities to sodium trifluoroacetate.

Trifluoroacetate (100 mu

M-3 mM) enhanced the currents elicited by low concentrations of glycine applied to alpha 1 homomeric and alpha 1 Gemcitabine cell line beta heteromeric glycine receptors, but it had no effects when co-applied with a maximally-effective glycine concentration. Trifluoroacetate had no effects on alpha 1 beta 2 gamma 2S GABA(A) or 5-HT3A receptors at any GABA or serotonin concentration tested.

The results demonstrate that trifluoroacetate acts as an allosteric modulator at the glycine receptor with greater specificity than other known modulators. These results have important implications for both the secondary effects of volatile anesthetics and the presence of contaminating trifluoroacetate in HPLC-purified peptides, which is potentially an important source of experimental variability or error that requires control. (C) 2012 Elsevier Ltd. All rights reserved.”
“Metabolic labeling of plant tissues with N-15 has become widely used in plant proteomics. Here, we describe a robust experimental design and data analysis workflow implementing two parallel biological replicate experiments with reciprocal labeling and series of 1:1 control mixtures. Thereby, we are able to unambiguously distinguish (i) inherent biological variation between cultures and (ii) specific responses to a biological treatment. The data analysis workflow is based on first determining the variation between cultures based on N-15/N-14 ratios in independent 1:1 mixtures before biological treatment is applied.

Resource depletion through division is also the major determinant

Resource depletion through division is also the major determinant of the stability of polyandry, whereas relatedness between co-husbands is not essential. Finally, I show that when females control the transfer of their own resources, monogamy is stable under more general conditions than previously believed. (C) 2012 Elsevier Ltd. All rights

reserved.”
“Conventional anti-hapten antibodies typically bind low-molecular weight compounds (haptens) in the crevice between the variable heavy and light chains. Conversely, heavy chain-only camelid antibodies, which lack a light chain, must rely entirely on a single variable domain to recognize haptens. While several anti-hapten VHHs have been generated, little is known regarding the underlying U0126 structural and thermodynamic

basis for hapten recognition. Here, an anti-methotrexate VHH (anti-MTX VHH) was generated using grafting methods whereby the three complementarity determining regions (CDRs) Pevonedistat supplier were inserted onto an existing VHH framework. Thermodynamic analysis of the anti-MTX VHH CDR1-3 Graft revealed a micromolar binding affinity, while the crystal structure of the complex revealed a somewhat surprising noncanonical binding site which involved MTX tunneling under the CDR1 loop. Due to the close proximity of MTX to CDR4, a nonhypervariable loop, the CDR4 loop sequence was subsequently introduced into the CDR1-3 graft, which resulted in a dramatic 1000-fold increase in the binding affinity. Crystal structure analysis of both the free and complex anti-MTX CDR1-4 graft revealed CDR4 plays a significant role in both intermolecular contacts and

binding site conformation that appear to contribute toward high affinity binding. Additionally, the anti-MTX VHH possessed relatively high specificity for MTX over closely related compounds aminopterin and folate, demonstrating that VHH domains are capable of binding low-molecular weight ligands with high affinity and specificity, despite their reduced interface.”
“There is Dapagliflozin a high prevalence of sialic acid in a number of different organisms, resulting in there being a myriad of different enzymes that can exploit it as a fermentable carbon source. One such enzyme is NanS, a carbohydrate esterase that we show here deacetylates the 9 position of 9-O-sialic acid so that it can be readily transported into the cell for catabolism. Through structural studies, we show that NanS adopts a SGNH hydrolase fold. Although the backbone of the structure is similar to previously characterized family members, sequence comparisons indicate that this family can be further subdivided into two subfamilies with somewhat different fingerprints. NanS is the founding member of group II. Its catalytic center contains Ser19 and His301 but no Asp/Glu is present to form the classical catalytic triad. The contribution of Ser19 and His301 to catalysis was confirmed by mutagenesis.

These biomarkers were confirmed in a blinded assessment of additi

These biomarkers were confirmed in a blinded assessment of additional samples. The blinded click here data also revealed time-dependency of induced changes. Some of the potential biomarkers could be sequenced. This information revealed great similarity between cis-Platin-induced changes and significant changes in the urinary proteome of patients suffering from tubular injury (Fanconi syndrome). Our study strongly suggests that (drug-induced) nephrotoxicity can be detected with high accuracy in laboratory rodents using urinary proteome analysis. The effects observed are very similar to those seen in corresponding human diseases and similar approaches may be very

helpful in evaluating drug-induced organ damage in preclinical animal models. This study aiming at the definition of biomarkers for drug-induced cytotoxicity may serve as a proof-of-principle for the use of urinary proteomics selleck kinase inhibitor in assessment of drug-induced nephrotoxicity.”
“BACKGROUND: Protection techniques using stents or microcatheters allow treatment of aneurysms with complex configurations by coil embolization. However, the application of these techniques is occasionally limited in wide-neck middle cerebral artery (MCA) aneurysms with acute angularity of the efferent branch vessel.

OBJECTIVE:

We describe a looping technique for passage of a microcatheter and microwire into the acutely angled efferent branch vessel without navigating the system through the aneurysm lumen.

METHODS: To select the acutely angulated branch, a looped microcatheter was advanced near the orifice of the distal acutely angled branch learn more vessel, followed by microwire passage through the looped microcatheter into the efferent vessel. The microcatheter loop was straightened after the microwire had been sufficiently advanced. The

microcatheter was then navigated into the distal branch vessel over the advanced microwire.

RESULTS: A total of 36 wide-neck MCA aneurysms were successfully treated using this looping method. This technique was used to pass the microcatheter for stent protection in 13 patients and for microcatheter protection in 23. The method was most commonly used for aneurysms located at the M1 trunk (n = 21), followed by the MCA bifurcation (n = 15). Complete or near-complete endosaccular occlusion was achieved in 31 aneurysms. There were no complications related to looping the microcatheter.

CONCLUSION: This microcatheter looping technique facilitates safe entry into the distal branch during coil embolization of wide-neck MCA aneurysms incorporating the origins of acutely angulated branches.”
“The recent outbreak of enterovirus 71 (EV71) infected millions of children and caused over 1,000 deaths.

In longitudinal studies where walking and health are ascertained

In longitudinal studies where walking and health are ascertained at every wave, limited-bias estimates can provide better estimates of the benefits of walking. A surprisingly small increase in walking was associated with meaningful BIX 1294 health benefits.”
“Introduction:

PET imaging in plants is receiving increased interest as a new strategy to measure plant responses to environmental stimuli and as a tool for phenotyping genetically engineered plants. PET imaging in plants, however, poses new challenges. In particular, the leaves of most plants are so thin that a large fraction of positrons emitted from PET isotopes ((18)F, (11)C, (13)N) escape while even state-of-the-art PET cameras have significant partial-volume errors for such thin objects. Although these limitations are acknowledged by researchers, little data have been published on them.

Methods: Here we measured the magnitude and distribution of escaping positrons from the leaf of Nicotiana tabacum for the radionuclides (18)F, (11)C and (13)N using a commercial small-animal PET scanner. Imaging results were compared to radionuclide concentrations measured

from dissection and counting and to a Monte Carlo simulation using GATE (Geant4 Application for Tomographic Emission).

Results: Simulated and experimentally determined escape fractions were consistent. The fractions of positrons (mean +/- S.D.) escaping the leaf parenchyma were measured to be 59 +/- 1.1%, 64 +/- 4.4% and 67 +/- 1.9% for (18)F, (11)C and (13)N, respectively. Escape fractions were lower in thicker

mTOR inhibitor leaf areas like the midrib. Partial-volume averaging underestimated activity concentrations in the leaf blade by a factor of 10 to 15.

Conclusions: The foregoing effects combine to yield PET images whose contrast does not reflect the actual activity concentrations. These errors can be largely corrected by integrating activity along the PET axis perpendicular to the leaf surface, including detection of escaped positrons, and calculating concentration using a measured leaf thickness. (C) 2011 Elsevier Inc. All rights reserved.”
“Balance is among the most important prerequisites for safe and independent mobility. Whether musculoskeletal DCLK1 pain is related to standing balance impairment has received limited attention. The aim of this study was to examine the association of musculoskeletal pain with the control of balance in older people.

A total of 605 participants aged 75 years and older (mean age 80.4, 71 % women) were interviewed about presence and severity of musculoskeletal pain. Balance was measured by a force platform, and impaired balance was defined as a high sway velocity moment or inability to maintain semitandem standing.

Musculoskeletal pain was reported by 48% of the participants, of whom majority had moderate to severe pain in lower extremities or back.

Our model of radiogenic oxidative stress is consistent with these

Our model of radiogenic oxidative stress is consistent with these data and can potentially be generalized to other organisms and lower radiation doses. (C) 2009 Elsevier Ltd. All rights reserved.”
“Evidence of normalized auditory P50 suppression with acute nicotine in schizophrenia has supported the contention that elevated smoking rates in this disorder may be an attempt to correct a nicotinic receptor

pathophysiology that may underly impaired sensory gating in these patients. There is very little information regarding the neurochemical or genetic pathways through which nicotine regulates P50 amplitude and its suppression in human studies. In a randomized, double-blind, placebo-controlled design with 24 non-smokers, this study examined the influence of TaqIA dopamine LCL161 manufacturer D2 receptor gene polymorphisms on P50 and its inhibition during nicotine gum (6 mg) administration. Within a paired click (S(1)-S(2)) paradigm, placebo treated A1(+) and A1(-) allele groups differed with respect

to P50 amplitude and gating. While nicotine (relative to placebo) attenuated S, P50 amplitude BI-D1870 manufacturer in A1(+) allele carriers, in the A1(-) carriers it increased S(2) P50 amplitude and increased P50 gating as indexed by an augmented gating difference wave (GDW). These findings suggest that nicotine exerts mixed gating properties in healthy nicotine naive volunteers and that dopamine functions to alter both P50 and its gating as D-malate dehydrogenase well as their response to acute nicotine agonist treatment. (C) 2010 IBRO. Published by Elsevier Ltd. All rights reserved.”
“Hypoxia-ischemia is a significant cause of brain damage in the human newborn and can result in long-term neurodevelopmental disability. The loss of oxygen and glucose supply to the developing brain leads to excitotoxic neuronal cell damage and

death; such over-excitation of nerve cells can also manifest as seizures. The newborn brain is highly susceptible to seizures although it is unclear what role they have in hypoxic-ischemic (H/I) injury. The aim of this study was to determine an association between seizures and severity of brain injury in a piglet model of perinatal H/I and, whether injury severity was related to type of seizure, i.e. sub-clinical (electrographic seizures only) or clinical (electrographic seizures+physical signs). Hypoxia (4% O(2)) was induced in anaesthetised newborn piglets for 30 min with a final 10 min period of hypotension; animals were recovered and survived to 72 h. Animals were monitored daily for seizures both visually and with electroencephalogram (EEG) recordings. Brain injury was assessed with magnetic resonance imaging (MRI), (1)H-MR spectroscopy ((1)H-MRS), EEG and by histology (haematoxylin and eosin). EEG seizures were observed in 75% of all H/I animals, 46% displayed clinical seizures and 29% sub-clinical seizures. Seizure animals showed significantly lower background amplitude EEG across all post-insult days.